A Phase II, Open-Label, Multicenter Study of Capmatinib in Subjects With MET Exon 14 Skipping Mutation Positive, Advanced, NSCLC With Brain Metastases

Non-small Cell Lung Carcinoma (NSCLC) Clinical Trial

Official title: A Phase II, Open-Label, Multicenter Study of Capmatinib in Subjects With MET Exon 14 Skipping Mutation Positive, Advanced, Non Small-Cell Lung Cancer That Has Metastasized to the Brain

Status Withdrawn

Clinical Trial Summary

The purpose of this study is to establish the intracranial efficacy of single agent capmatinib in the population of treatment-naïve or pretreated with one or two prior lines of systemic therapies for advanced stage Non Small-Cell Lung Cancer (NSCLC) with MET exon 14 mutation that has metastasized to the brain.

Cohort 1 (asymptomatic brain metastases (BM) without prior brain therapy) has been selected to identify patients who are most likely to benefit from capmatinib therapy in this setting and to establish a clinically relevant response outcome.

Cohort 2 is a heterogeneous group of patients (symptomatic with and without prior brain therapy, asymptomatic with prior brain therapy, or with leptomeningeal disease.), and the outcomes will be descriptive only

Clinical Trial Description

This is a prospectively designed, multicenter, open-label, two-cohort, phase II study to evaluate the intracranial efficacy of single agent capmatinib in participants with MET exon 14 mutated NSCLC and BM. Participants can be treatment naïve or pretreated with one or two prior lines of systemic therapies for advanced stage (stage IIIb - IV) NSCLC.

Approximately 60 participants will be enrolled globally and allocated to one of two cohorts:

Cohort 1 will enroll approximately 40 participants who are asymptomatic and without prior brain therapy.

Cohort 2 will enroll approximately 20 participants who are symptomatic with or without prior brain therapy or asymptomatic with prior brain therapy or with leptomeningeal disease.

All participants will be pre-screened for MET mutation and presence of BM will be documented at baseline by a radiologist/neuroradiologist.

Intracranial disease will be assessed and response to treatment will be evaluated using the Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria every 8 weeks. Extracranial and whole body disease will be assessed and response to treatment will be evaluated using RECIST 1.1 every 8 weeks.

Participants will receive capmatinib 400 mg b.i.d. until they experience any of the following: documented disease progression by RANO-BM criteria and/or RECIST 1.1 (as assessed by the investigator and confirmed by BIRC), withdrawal of consent, pregnancy, lost to follow-up, or death.

For all participants, treatment with capmatinib may be continued beyond initial progression disease (PD) as per RANO-BM criteria and/or RECIST 1.1 (as assessed by the investigator and confirmed by BIRC) if, in the judgment of the investigator, there is evidence of clinical benefit, and the participant wishes to continue on the study treatment.

After treatment discontinuation, all participants will be followed for safety evaluations during the safety follow-up period, and the participant's status will be collected every 12 weeks as part of the survival follow-up. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Carcinoma (NSCLC)

• NCT number: NCT04460729
• Study type: Interventional
• Source: Novartis
• Status: Withdrawn
• Phase: Phase 2
• Start date: November 11, 2020
• Completion date: November 17, 2023